Bilirubin Molecular Species Play an Important Role in the Pathophysiology of Acute-on-Chronic Liver Failure.

Bilirubin plays a key role in early diagnosis, prognosis, and prevention of liver diseases. Unconjugated bilirubin (UCB) requires conversion to a water-soluble form through liver glucuronidation, producing monoglucuronide (BMG) or diglucuronide bilirubin (BDG) for bile excretion. This study aimed to assess the roles of bilirubin's molecular species-UCB, BMG, and BDG-in diagnosing and understanding the pathogenesis of liver cirrhosis in patients with acute-on-chronic liver failure (ACLF), compensated liver cirrhosis (LC) patients, and healthy individuals. The study included patients with ACLF and compensated LC of diverse etiologies, along with healthy controls. We collected laboratory and clinical data to determine the severity and assess mortality. We extracted bilirubin from serum samples to measure UCB, BMG, and BDG using liquid chromatography-mass spectrometry (LC-MS). The quantification of bilirubin was performed by monitoring the mass charge (m/z) ratio. Of the 74 patients assessed, 45 had ACLF, 11 had LC, and 18 were healthy individuals. Among ACLF patients, the levels of molecular species of bilirubin were UCB 19.69 µmol/L, BMG 47.71 µmol/L, and BDG 2.120 µmol/L. For compensated cirrhosis patients, the levels were UCB 11.29 µmol/L, BMG 1.49 µmol/L, and BDG 0.055 µmol/L, and in healthy individuals, the levels were UCB 6.42 µmol/L, BMG 0.52 µmol/L, and BDG 0.028 µmol/L. The study revealed marked elevations in the bilirubin species in individuals with ACLF compared to those with compensated cirrhosis and healthy controls, underscoring the progression of liver dysfunction. The correlation of BMG and BDG levels with commonly used inflammatory markers suggests a relationship between bilirubin metabolism and systemic inflammation in ACLF.

The Immunoregulatory and Regenerative Potential of Activated Human Stem Cell Secretome Mitigates Acute-on-Chronic Liver Failure in a Rat Model.

Acute-on-chronic liver failure (ACLF) is a syndrome marked by sudden liver function decline and multiorgan failure, predominantly acute kidney injury (AKY), in patients with chronic liver disease. Unregulated inflammation is a hallmark of ACLF; however, the key drivers of ACLF are not fully understood. This study explores the therapeutic properties of human mesenchymal stem cell (MSC) secretome, particularly focusing on its enhanced anti-inflammatory and pro-regenerative properties after the in vitro preconditioning of the cells. We evaluated the efficacy of the systemic administration of MSC secretome in preventing liver failure and AKI in a rat ACLF model where chronic liver disease was induced using by the administration of porcine serum, followed by D-galN/LPS administration to induce acute failure. After ACLF induction, animals were treated with saline (ACLF group) or MSC-derived secretome (ACLF-secretome group). The study revealed that MSC-secretome administration strongly reduced liver histological damage in the ACLF group, which was correlated with higher hepatocyte proliferation, increased hepatic and systemic anti-inflammatory molecule levels, and reduced neutrophil and macrophage infiltration. Additionally, renal examination revealed that MSC-secretome treatment mitigated tubular injuries, reduced apoptosis, and downregulated injury markers. These improvements were linked to increased survival rates in the ACLF-secretome group, endorsing MSC secretomes as a promising therapy for multiorgan failure in ACLF.

Albúmina en cirrosis: perspectiva inflamatoria / Albumin in cirrhosis: inflammatory perspective

La albúmina sérica humana es la proteína más abundante en el plasma, su estructura molecular le confiere estabilidad, pero también flexibilidad para ligar y transportar un amplio rango de moléculas. Su función oncótica es la propiedad más reconocida que la lleva a introducirse en la terapéutica médica como un expansor de volumen. Sin embargo, en los últimos años se le han adicionado funciones con carácter antioxidante, inmunomodulador y de estabilización endotelial, que hacen presumir que su impacto terapéutico está más allá de sus funciones volumétricas. En los últimos años, específicamente en la cirrosis y la falla hepática aguda sobre crónica, se ha tenido un cambio en el paradigma fisiológico, desde una perspectiva netamente hemodinámica hacia una perspectiva inflamatoria, en donde las funciones oncóticas y no oncóticas de la albúmina están alteradas y tienen un carácter pronóstico en estas entidades. Este conocimiento creciente, desde una perspectiva inflamatoria, hace que se fortalezca el uso terapéutico de la albúmina sérica humana desde las indicaciones tradicionales como prevención de la disfunción circulatoria posparacentesis, prevención y tratamiento de lesión renal aguda, hasta las discusiones para administración a largo plazo en pacientes cirróticos con ascitis.

Human serum albumin is the most abundant protein in plasma, with a molecular structure that provides stability while also allowing flexibility to bind and transport a wide range of molecules. Its oncotic function is the most recognized property, leading to its introduction in medical therapy as a volume expander. However, in recent years, additional functions with antioxidant, immunomodulatory, and endothelial stabilization properties have been identified, suggesting that its therapeutic impact extends beyond its volumetric functions. Specifically, in cirrhosis and acute-on-chronic liver failure, there has been a shift in the pathophysiological paradigm from a purely hemodynamic perspective to an inflammatory perspective, where both oncotic and non-oncotic functions of albumin are altered and have prognostic significance in these conditions. This growing understanding from an inflammatory perspective strengthens the therapeutic use of human serum albumin, not only for traditional indications such as the prevention of post-paracentesis circulatory disfunction, prevention and treatment of acute kidney injury, but also for discussions regarding long-term administration in cirrhotic patients with ascites.

Acute-on-chronic liver failure: a retrospective review of cases at a transplantation center in Brazil

Purpose: Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver transplantation (LT) center in Brazil. Methods: Retrospective study analyzing patient data from 2017 to 2022. Re-transplant cases and patients without previous chronic liver disease were excluded. The ACLF diagnosis was based on the European Association for the Study of the Liver-Chronic Liver Failure criteria and assessments repeated on days 3 and 7 after the initial diagnosis. Results: Among 381 patients, 10.49% (n = 40) were diagnosed with ACLF. Bacterial infection was the most common precipitating factor (45%). Kidney failure occurred in 65% of the cases. The 28-day mortality rate was 35% and varied according to ACLF severity at diagnosis, from single organ failure (ACLF-1) at 22% to three organ failures (ACLF-3) at 60%. Eighteen patients (45%) were transplanted with a 100% 28-day survival rate. For ACLF-3 cases at diagnosis (n = 15), the 28-day and 1-year survival rates with a transplant (n = 4) were 100% and 80%, respectively, and without transplant (n = 11), 10 and 0%, respectively. Conclusions: ACLF was associated with high mortality rates. LT was an effective therapeutic option, particularly for ACLF-3 cases.

Effect of acute on chronic liver failure over post-transplant survival.

INTRODUCTION AND OBJECTIVES: Acute-on-chronic liver failure (ACLF) is associated with reduced short-term survival, and liver transplantation is frequently the only therapeutic option. Nonetheless, the post-transplantation prognosis seems to be worse in ACLF patients. MATERIALS AND METHODS: The databases of two university centers were retrospectively evaluated, and adult patients with cirrhosis who underwent transplantation between 2013 and 2020 were included. One-year survival of patients with ACLF was compared to that of patients without ACLF. Variables associated with mortality were identified. RESULTS: A total of 428 patients were evaluated, and 303 met the inclusion criteria; 57.1% were male, the mean age was 57.1 ± 10.2 years, 75 patients had ACLF, and 228 did not. The main etiologies of ACLF were NASH (36.6%), alcoholic liver disease (13.9%), primary biliary cholangitis (8.6%) and autoimmune hepatitis (7.9%). Mechanical ventilation, renal replacement therapy, the use of vasopressors and the requirement of blood product transfusion during liver transplantation were significantly more frequent in ACLF patients. Among those recipients without and with ACLF, survival at 1, 3 and 5 years was 91.2% vs. 74.7%, 89.1% vs. 72.6% and 88.3% vs. 72.6%, respectively (p=0.001). Among pre-transplantation variables, only the presence of ACLF was independently associated with survival (HR 3.2, 95% CI: 1.46-7.11). Post-transplantation variables independently associated with survival were renal replacement therapy (HR 2.8, 95% CI: 1.1-6.8) and fungal infections (HR 3.26, 95% CI: 1.07-9.9). CONCLUSIONS: ACLF is an independent predictor of one-year post-transplantation survival. Importantly, transplant recipients with ACLF require the use of more resources than patients without ACLF.

Acute-on-chronic liver failure is independently associated with higher mortality for cirrhotic patients with acute esophageal variceal hemorrhage: Retrospective cohort study.

BACKGROUND: Acute esophageal variceal hemorrhage (AEVH) is a common complication of cirrhosis and might precipitate multi-organ failure, causing acute-on-chronic liver failure (ACLF). AIM: To analyze if the presence and grading of ACLF as defined by European Society for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) is able to predict mortality in cirrhotic patients presenting AEVH. METHODS: Retrospective cohort study executed in Hospital Geral de Caxias do Sul. Data from medical records from 2010 to 2016 were obtained by searching the hospital electronic database for patients who received terlipressin. Medical records were reviewed in order to determine the diagnosis of cirrhosis and AEVH, including 97 patients. Kaplan-Meier survival analysis was used for univariate analysis and a stepwise approach to the Cox regression for multivariate analysis. RESULTS: All- cause mortality for AEVH patients was 36%, 40.2% and 49.4% for 30-, 90- and 365-day, respectively. The prevalence of ACLF was 41.3%. Of these, 35% grade 1, 50% grade 2 and 15% grade 3. In multivariate analysis, the non-use of non-selective beta-blockers, presence and higher grading of ACLF and higher Model for End-Stage Liver Disease scores were independently associated with higher mortality for 30-day with the addition of higher Child-Pugh scores for 90-day period. CONCLUSION: Presence and grading of ACLF according to the EASL-CLIF criteria was independently associated with higher 30- and 90-day mortality in cirrhotic patients admitted due to AEVH.

Falla hepática aguda sobre crónica / Acute on chronic liver failure

La falla hepática aguda sobre crónica (ACLF) es un síndrome que se presenta en pacientes con cirrosis descompensada, y se caracteriza por una mortalidad elevada a 28 días, que se diagnostica con la combinación de falla hepática y extrahepática. Se han publicado numerosas definiciones, de las cuales se resalta la realizada por la Asociación Europea para el Estudio del Hígado (EASL), la cual tiene en cuenta 6 sistemas orgánicos (hígado, riñón, pulmón, cerebro, coagulación y circulación), y gradúa su gravedad basada en el número de sistemas comprometidos en el momento de la presentación. Entre los pilares en el abordaje del paciente con ACLF es imperiosa la búsqueda de los factores precipitantes, siendo los más frecuentes las infecciones bacterianas, el consumo excesivo de alcohol, la hemorragia de vías digestivas, la injuria hepática inducida por medicamentos y la cirugía hepática o cirugía mayor, teniendo en cuenta que aproximadamente en el 50 % de los casos no se logrará establecer la causa. Los pilares angulares del tratamiento constarán de la reversión o interrupción del factor precipitante, el soporte orgánico y, en aquellos pacientes que cumplan los criterios para trasplante, su realización oportuna.

Acute-on-chronic liver failure is a syndrome that occurs in patients with acute decompensated cirrhosis and is characterized by high 28-day mortality that is diagnosed with a combination of hepatic and extrahepatic organ failure. Numerous definitions have been published with great concern related to the etiology and cause of the decompensation, of which the one made by the European Association for the Study of the Liver (EASL) stands out, taking into account 6 organic systems (liver, kidney, lung, brain, coagulation, and circulation), and grades its severity based on the number of systems involved at the time of presentation. Among the pillars in the approach to the patient with ACLF, the search for precipitating factors is imperative, the most frequent being bacte-rial infections, excessive alcohol consumption, digestive tract bleeding, drug-induced liver injury, liver surgery or major surgery, keeping in mind that in approximately 50% of cases the cause will not be established. The cornerstones of treatment will consist of the reversal or interruption of the precipitating factor, organ support and, in those patients who meet the criteria for transplantation, its timely performance.

Elevated calprotectin levels are associated with mortality in patients with acute decompensation of liver cirrhosis.

BACKGROUND: Acute decompensation (AD) of cirrhosis is related to systemic inflammation and elevated circulating cytokines. In this context, biomarkers of inflammation, such as calprotectin, may be of prognostic value. AIM: To evaluate serum calprotectin levels in patients hospitalized for complications of cirrhosis. METHODS: This is a prospective cohort study that included 200 subjects hospitalized for complications of cirrhosis, 20 outpatients with stable cirrhosis, and 20 healthy controls. Serum calprotectin was measured by enzyme-linked immunosorbant assay. RESULTS: Calprotectin levels were higher among groups with cirrhosis when compared to healthy controls. Higher median calprotectin was related to Child-Pugh C, ascites, and hepatic encephalopathy. Higher calprotectin was related to acute-on-chronic liver failure (ACLF) and infection in the bivariate, but not in multivariate analysis. Calprotectin was not associated with survival among patients with ACLF; however, in patients with AD without ACLF, higher calprotectin was associated with a lower 30-d survival, even after adjustment for chronic liver failure-consortium (CLIF-C) AD score. A high-risk group (CLIF-C AD score ≥ 60 and calprotectin ≥ 580 ng/mL) was identified, which had a 30-d survival (27.3%) similar to that of patients with grade 3 ACLF (23.3%). CONCLUSION: Serum calprotectin is associated with prognosis in patients with AD without ACLF and may be useful in clinical practice to early identify patients with a very low short-term survival.

Public Health Measures and Prevention of Alcohol-Associated Liver Disease.

Hazardous alcohol consumption causes approximately 4% of deaths globally, constituting one of the leading risk factors for the burden of the disease worldwide. Alcohol has several health consequences, such as alcohol-associated liver disease, hepatocellular carcinoma, nonliver neoplasms, physical injury, cardiac disease, and psychiatric disorders. Alcohol misuse significantly affects workforce productivity, with elevated direct and indirect economic costs. Due to the high impact of alcohol consumption on the population, public health has led to the development of a range of strategies to reduce its harmful effects. Regulatory public health policies (PHP) for alcohol can exist at the global, regional, international, national, or subnational levels. Effective strategies incorporate a multilevel, multicomponent approach, targeting multiple determinants of drinking and alcohol-related harms. The World Health Organization categorizes the PHP into eight categories: national plan to fight the harmful consequences of alcohol, national license and production and selling control, taxes control and pricing policies, limiting drinking age, restrictions on alcohol access, driving-related alcohol policies, control over advertising and promotion, and government monitoring systems. These policies are supported by evidence from different populations, demonstrating that determinants of alcohol use depend on several factors such as socioeconomic level, age, sex, ethnicity, production, availability, marketing, and others. Although most policies have a significant individual effect, a higher number of PHP are associated with a lower burden of disease due to alcohol. The excessive consequences of alcohol constitute a call for action, and clinicians should advocate for developing and implementing a new PHP on alcohol consumption.

Liver transplantation is beneficial regardless of cirrhosis stage or acute-on-chronic liver failure grade: A single-center experience.

BACKGROUND: Liver transplantation for the most critically ill remains controversial; however, it is currently the only curative treatment option. AIM: To assess immediate posttransplant outcomes and compare the short (1 year) and long-term (6 years) posttransplant survival among cirrhotic patients stratified by disease severity. METHODS: We included cirrhotic patients undergoing liver transplantation between 2015 and 2019 and categorized them into compensated cirrhosis (CC), decompensated cirrhosis (DC), and acute-on-chronic liver failure (ACLF). ACLF was further divided into severity grades. Our primary outcomes of interest were total days of intensive care unit (ICU) and hospital stay, development of complications and posttransplant survival at 1 and 6 years. RESULTS: 235 patients underwent liver transplantation (CC = 11, DC = 129 and ACLF = 95). Patients with ACLF had a significantly longer hospital stay [8.0 (6.0-13.0) vs CC, 6.0 (3.0-7.0), and DC 7.0 (4.5-10.0); P = 0.01] and developed more infection-related complications [47 (49.5%), vs CC, 1 (9.1%) and DC, 38 (29.5%); P < 0.01]. Posttransplant survival at 1- and 6-years was similar among groups (P = 0.60 and P = 0.90, respectively). ACLF patients stratified according to ACLF grade [ACLF-1 n = 40 (42.1%), ACLF-2 n = 33 (34.7%) and ACLF-3 n = 22 (23.2%)], had similar ICU and hospital stay length (P = 0.68, P = 0.54), as well as comparable frequencies of overall and infectious post-transplant complications (P = 0.58, P = 0.80). There was no survival difference between ACLF grades at 1 year and 6 years (P = 0.40 and P = 0.15). CONCLUSION: Patients may benefit from liver transplantation regardless of the cirrhosis stage. ACLF patients have a longer hospital stay and frequency of infectious complications; however, excellent, and comparable 1 and 6-year survival rates support their enlisting and transplantation including those with ACLF-3.

Diálisis de albúmina de paso único (SPAD) como soporte hepático extracorpóreo en paciente COVID-19 crítico. Caso clínico / Single-pass albumin dialysis as treatment of acute on chronic liver failure during COVID-19 pneumonia. report of one case

Liver transplantation is the only effective therapy to reduce the high mortality associated with acute liver failure and acute on chronic liver failure (ACLF). Single-pass albumin dialysis (SPAD) is an extracorporeal supportive therapy used as a bridge to liver transplantation or regeneration. We report a 44-year-old man with alcoholic cirrhosis admitted for critical COVID-19 pneumonia that evolves with ACLF. SPAD technique was performed completing six sessions, with a reduction of bilirubin and ammonia levels. He evolved with severe respiratory failure and refractory septic shock, dying. SPAD is a safe and efficient technique aimed to eliminate liver toxins, preventing multiorgan damage interrupting the process known as the "autointoxication hypothesis". It is easy to implement in any critical patient unit and has lower costs than other extracorporeal liver support therapies.

[Cutaneous hyperpigmentation as a manifestation in acute on chronic liver failure]. / Hiperpigmentación cutánea como manifestación poco reconocida en falla hepática aguda sobre crónica.

Background: The acquired cutaneous pigmentation represents a little recognized clinical manifestation in liver disorders, both acute and chronic, and can occur in the exacerbation processes of preexisting hepatopathies, as in the context of acute-on-chronic liver failure. Several hypotheses about the increase in pigment at skin and mucous membranes have been developed; some try to explain it as a defect in the degradation of melanin with secondary accumulation at tissues; others, on the other hand, describe it as a consequence of the release of fibroblast growth factors like endothelial growth factor and hepatocyte growth factor, which are produced under the stimulation of liver regeneration and cause a melanogenesis stimulation. The aim of this article is to study pigmentary skin changes in the background of liver diseases. Clinical cases: We described two clinical cases of patients with acuteon chronic liver failure secondary to different clinical scenarios are presented, who have in common the development of acquired pigmentary skin changes. Conclusion: In hepatopathies, the cutaneous hyperpigmentation is a sign with unknown etiology, so further studies are required to know the accurate pathophysiology. Reporting this finding is useful for physicians, since timely identification can help in the early diagnosis of underlying liver diseases.

Introducción: la hiperpigmentación cutánea adquirida representa una manifestación clínica poco reconocida en los trastornos hepáticos, tanto agudos como crónicos, y puede presentarse tanto en procesos de agudización de hepatopatías preexistentes como en el contexto de la falla hepática aguda sobre crónica. Se han desarrollado diversas hipótesis sobre el aumento de pigmento a nivel piel y mucosas, algunas tratan de explicarlo por un defecto en la degradación de la melanina, lo cual genera su acumilación en los tejidos; otras, en cambio, describen la liberación de factores de crecimiento derivados de fibroblastos, como el factor de crecimiento endotelial y el factor de crecimiento de hepatocitos, los cuales son producidos bajo el estímulo de la regeneración hepática y, a su vez, provocan una estimulación de la melanogénesis. El objetivo de este trabajo es estudiar la hiperpigmentación cutánea en el contexto de enfermedades hepáticas. Casos clínicos: se presentan dos casos clínicos de pacientes con falla hepática aguda sobre crónica secundaria a diferentes escenarios clínicos, quienes tienen en común el desarrollo pigmentación cutánea adquirida. Conclusiones: en las enfermedades hepáticas, la hiperpigmentación cutánea es un hallazgo presente cuya etiología aún no es dilucidada, por lo que se requieren más estudios para conocer la fisiopatología exacta. El reporte de este hallazgo es de utilidad para el personal médico, ya que la identificación oportuna puede ayudar a el diagnóstico temprano de hepatopatías subyacentes.

Current Medical Treatment for Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

Galectin-3 is overexpressed in advanced cirrhosis and predicts post-liver transplant infectious complications.

BACKGROUND & AIMS: Patients with advanced cirrhosis often have immune dysfunction and are more susceptible to infections. Galectin-3 is a ß-galactoside-binding lectin implicated in inflammation, immune regulation and liver fibrosis. We aim to investigate galectin-3 expression in advanced cirrhosis and its ability to predict post-transplant infectious complications. METHODS: We collected sera and liver samples from 129 cirrhotic patients at the time of liver transplantation and from an external cohort of 37 patients with alcoholic liver disease including alcoholic hepatitis (AH) at the time of diagnosis. Galectin-3 was assessed by ELISA, real-time PCR, immunohistochemistry and RNA-seq. Receiver operating characteristic curves and Cox proportional-hazards regression analysis were performed to assess the predictive power of galectin-3 for disease severity and post-transplant infections. RESULTS: Increased galectin-3 levels were found in advanced cirrhosis. Galectin-3 significantly correlated with disease severity parameters and inflammatory markers. Galectin-3 had significant discriminating power for compensated and advanced cirrhosis (AUC = 0.78/0.84, circulating/liver galectin-3; p < .01), and was even higher to discriminate severe AH (AUC = 0.95, p < .0001). Cox Proportional-hazard model showed that galectin-3, MELD-Na and the presence of SIRS predict the development of post-transplant infectious complications. Patients with circulating galectin-3 (>16.58 ng/ml) were at 2.19-fold 95% CI (1.12-4.29) increased risk, but when combined with MELD-Na > 20.0 and SIRS, the risk to develop post-transplant infectious complications, increased to 4.60, 95% CI (2.38-8.90). CONCLUSION: Galectin-3 is a novel biological marker of active inflammation and disease severity that could be clinically useful alone or in combination with other scores to discriminate advanced cirrhosis and predict post-transplant infectious complications.

Position statement on the use of albumin in liver cirrhosis.

Cirrhosis is characterised by a prolonged asymptomatic period in which the inflammation persists, increasing as the disease progresses. Characteristic of this is the increase in pro-inflammatory cytokines and pro-oxidant molecules which are determining factors in the development of multiple organ dysfunction. In the early development of cirrhosis, splanchnic arterial vasodilation, activation of vasoconstrictor systems (renin-angiotensin-aldosterone) and the sympathetic nervous system (noradrenaline) bring about bacterial translocation and systemic dissemination via portal circulation of bacterial products, and molecular patterns associated with damage, which exacerbate the systemic inflammation present in the patient with cirrhosis. Albumin is a molecule that undergoes structural and functional changes as liver damage progresses, affecting its antioxidant, immunomodulatory, oncotic and endothelial stabilising properties. Our knowledge of the properties of albumin reveals a molecule with multiple treatment options in patients with cirrhosis, from the compensated then decompensated phases to multiple organ dysfunction. Its recognised uses in spontaneous bacterial peritonitis, post-paracentesis circulatory dysfunction, acute kidney injury and hepatorenal syndrome are fully validated, and a treatment option has opened up in decompensated cirrhosis and in acute-on-chronic liver disease.

Animal models applied to acute-on-chronic liver failure: Are new models required to understand the human condition?

The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.

Current and future perspectives on acute-on-chronic liver failure: Challenges of transplantation, machine perfusion, and beyond.

Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation, organ failure and high short-term mortality. Partially due to the lack of universal diagnostic criteria, the actual ACLF prevalence remains unclear; nevertheless, it is expected to be a highly prevalent condition worldwide. Earlier transplantation is an effective protective measure for selected ACLF patients. Besides liver trans-plantation, diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of ACLF therapy. Although new clinical specific therapies have been researched, more studies are necessary to assess safety and efficacy. Therefore, future ACLF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently narrow. Thus, an urgent and global discussion about allocation and prioritization for transplantation in critically ill ACLF patients is needed because there is evidence suggesting that the current model may not portray their waitlist mortality. In addition, while donor organ quality is meant to be a prognostic factor in the ACLF setting, recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.

Infecciones bacterianas no espontáneas en pacientes cirróticos hospitalizados, Hospital Central de las Fuerzas Armadas, marzo 2018-diciembre 2020

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Abstract: Introduction: Bacterial infections in cirrhotic patients are a frequent complication, which occurs mainly in advanced stages of the disease. Non-spontaneous infections or infections not related to portal hypertension include mainly those of the urinary tract, acute pneumonia, and skin and soft tissue infections. They generate a significant impact on the evolution of the disease, since they increase morbidity and mortality, and are also the most common precipitating factor of acute over chronic liver failure, a serious condition with high short-term mortality. The objective of this work is to know the incidence, and describe the clinical, epidemiological, microbiological, and evolutionary characteristics of non-spontaneous bacterial infections, in patients with liver cirrhosis, admitted to the Military Hospital, in the period between March 2018 and December 2020. Methodology: A cross-sectional, descriptive and single-center study was carried out, which included hospitalized patients, diagnosed with liver cirrhosis, who presented a bacterial infection not related to portal hypertension on admission or during hospital stay. Data were analyzed using frequency distribution and summary measures for the different variables. The incidence of non-spontaneous bacterial infections was calculated based on the total population of cirrhotic patients admitted during that period. Results: Of the total number of cirrhotic patients admitted, 17.5% had a bacterial infection not linked to portal hypertension, with a mean age of 61 years, 70% being men. The main etiology of cirrhosis was alcoholic. The vast majority of patients (95%) presented an advanced stage of liver disease (60% Child-Pugh stage B and 35% stage C), with a mean MELD-Na of 21. The most frequent infection was that of the urinary tract (50%), followed by acute pneumonia (20%), skin and soft tissue infections (10%) and acute cholangitis (10%). The most prevalent microorganisms were gram negative bacilli such as Klebsiella pneumoniae and Escherichia coli. 40% of the patients presented acute-on-chronic liver failure at the time of admission and an additional 5% developed it during evolution. Of this group of patients, 20% died during hospitalization. Conclusions: The present study constitutes an approximation to the knowledge of non-spontaneous infections in cirrhotic patients, being necessary the development of studies with a greater number of patients in order to establish a statistically significant association between the presence of bacterial infection and the development of acute on chronic liver failure, and from this with short-term mortality.

Resumo: Introdução: Infecções bacterianas em pacientes cirróticos são uma complicação frequente, que ocorre principalmente em estágios avançados da doença. Infecções não espontâneas ou infecções não relacionadas à hipertensão portal incluem principalmente aquelas do trato urinário, pneumonia aguda e infecções de pele e tecidos moles. Geram um impacto significativo na evolução da doença, pois aumentam a morbidade e a mortalidade, sendo também o fator precipitante mais comum da insuficiência hepática aguda sobre a crônica, uma condição grave com alta mortalidade em curto prazo. O objetivo deste trabalho é conhecer a incidência e descrever as características clínicas, epidemiológicas, microbiológicas e evolutivas das infecções bacterianas não espontâneas, em pacientes com cirrose hepática, internados no Hospital Militar, no período entre Março de 2018 e dezembro de 2020. Metodologia: Foi realizado um estudo transversal, descritivo e unicêntrico, que incluiu pacientes internados, com diagnóstico de cirrose hepática, que apresentavam infecção bacteriana não vinculada à hipertensão portal na admissão ou durante a internação. Os dados foram analisados ​​por meio de distribuição de frequência e medidas de resumo para as diferentes variáveis. A incidência de infecções bacterianas não espontâneas foi calculada com base na população total de pacientes cirróticos admitidos nesse período. Do total de cirróticos admitidos, 17,5% apresentavam infecção bacteriana não ligada à hipertensão portal, com média de idade de 61 anos, sendo 70% homens. A principal etiologia da cirrose foi alcoólica. A grande maioria dos pacientes (95%) apresentava doença hepática em estágio avançado (60% Child-Pugh estágio B e 35% estágio C), com média de MELD-Na de 21. A infecção mais frequente foi a do trato urinário (50%), seguida de pneumonia aguda (20%), infecções de pele e tecidos moles (10%) e colangite aguda (10%). Os microrganismos mais prevalentes foram bacilos gram negativos como Klebsiella pneumoniae e Escherichia coli. 40% dos pacientes apresentavam insuficiência hepática aguda-crônica no momento da admissão e outros 5% a desenvolveram durante a evolução. Desse grupo de pacientes, 20% morreram durante a internação. Conclusões: O presente estudo constitui uma aproximação ao conhecimento das infecções não espontâneas em pacientes cirróticos, sendo necessário o desenvolvimento de estudos com maior número de pacientes a fim de estabelecer uma associação estatisticamente significativa entre a presença de infecção bacteriana e o desenvolvimento de quadro agudo de insuficiência hepática crônica, e a partir disso com mortalidade a curto prazo.

Diagnósticos de enfermagem em pacientes com cirrose hepática em um serviço hospitalar de emergência / Nursing diagnoses in patients with liver cirrhosis in an emergency hospital service

Introdução: O estudo foi desenvolvido com o intuito de destacar a importância dos diagnósticos de enfermagem em pacientes cirróticos, em decorrência do aumento de casos de doenças hepáticas. Objetivo: Descrever as variáveis sociodemográficas e clínicas e elencar os diagnósticos de enfermagem da Associação Norte-Americana de Diagnósticos de Enfermagem (NANDA-I) em pacientes com cirrose hepática atendidos em uma emergência hospitalar. Material e Métodos: Pesquisa quantitativa, descritiva e transversal, realizada com 59 pacientes atendidos em uma emergência de um hospital universitário no sul do Brasil, no período de abril a junho de 2018. Resultados: Prevaleceu durante a pesquisa a população do sexo masculino com 66,1% e de baixo nível educacional, tendo o álcool como principal etiologia da doença com 44,1% e a presença de comorbidades como a hipertensão com 14,8% e o diabetes com 15,6%. Foram identificados seis diagnósticos de enfermagem com maior prevalência: risco de infecção, risco de desequilíbrio eletrolítico, nutrição desequilibrada (menor do que as necessidades corporais), dor aguda, volume de líquidos excessivo e risco de sangramento. Conclusão: As características sociodemográficas apresentadas neste estudo corroboram os achados já amplamente conhecidos em doença hepática. Os diagnósticos de enfermagem identificados foram condizentes com as repercussões fisiopatológicas da cirrose hepática, destacando-se o predomínio dos diagnósticos de risco.

Introduction: The study was developed with the aim of highlighting the importance of nursing diagnoses in cirrhotic patients, due to the increase in cases of liver disease. Objective: Describe the sociodemographic and clinical variables and list the nursing diagnoses of the North American Association of Nursing Diagnoses (NANDA-I) in patients with liver cirrhosis treated in a hospital emergency. Material and Methods: Quantitative, descriptive and cross-sectional research, conducted with 59 patients seen in an emergency department of a university hospital in southern Brazil, from April to June 2018. Results: There was a predominance during the research of the male population with 66.1% and of low educational level, with approximately 54.2% having completed elementary school, with alcohol as the main etiology of the disease with 44.1% and the presence of comorbidities such as hypertension with 14.8% and diabetes with 15.6%. Six nursing diagnoses with higher prevalence were identified: risk of infection, risk of electrolyte imbalance, unbalanced nutrition (less than body needs), acute pain, excessive fluid volume and risk of bleeding. Conclusion: The sociodemographic characteristics presented in this study corroborate the already widely known findings in liver disease. The nursing diagnoses identified were consistent with the pathophysiological repercussions of liver cirrhosis, highlighting the predominance of risk diagnoses.

Assessing the prognosis of cirrhotic patients in the intensive care unit: What we know and what we need to know better.

Critically ill cirrhotic patients have high in-hospital mortality and utilize significant health care resources as a consequence of the need for multiorgan support. Despite this fact, their mortality has decreased in recent decades due to improved care of critically ill patients. Acute-on-chronic liver failure (ACLF), sepsis and elevated hepatic scores are associated with increased mortality in this population, especially among those not eligible for liver transplantation. No score is superior to another in the prognostic assessment of these patients, and both liver-specific and intensive care unit-specific scores have satisfactory predictive accuracy. The sequential assessment of the scores, especially the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure Consortium (CLIF)-SOFA scores, may be useful as an auxiliary tool in the decision-making process regarding the benefits of maintaining supportive therapies in this population. A CLIF-ACLF > 70 at admission or at day 3 was associated with a poor prognosis, as well as SOFA score > 19 at baseline or increasing SOFA score > 72. Additional studies addressing the prognostic assessment of these patients are necessary.